Related Experiment Video
Updated: Jun 16, 2026
06:44
Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups
Published on: April 6, 2017
Selective deprotection of methanesulfonamides to amines
Hiroyuki Naito1, Takeshi Hata, Hirokazu Urabe
1Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
Organic Letters
|February 23, 2010
Summary
Methanesulfonamides can be converted to parent amines using oxygen and deprotonation. This method works even with other sulfonamides present, offering a new deprotection strategy.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Sulfonamides are common functional groups in organic chemistry.
- Deprotection of sulfonamides is a crucial step in many synthetic pathways.
- Existing methods for sulfonamide deprotection can be harsh or lack selectivity.
Purpose of the Study:
- To develop a novel and efficient method for the deprotection of methanesulfonamides.
- To explore the use of molecular oxygen as an oxidant in sulfonamide cleavage.
- To demonstrate the chemoselectivity of the developed method.
Main Methods:
- Deprotonation of methanesulfonamides using a suitable base.
- Oxygenation of the deprotonated intermediate with molecular oxygen (O(2) gas).
- Analysis of reaction products using standard organic chemistry techniques (e.g., NMR, Mass Spectrometry).
Main Results:
- Methanesulfonamides were successfully deprotected to their corresponding parent amines.
- The deprotection was achieved under mild conditions using O(2) as the oxidant.
- The method demonstrated excellent chemoselectivity, tolerating the presence of other sulfonamide types.
Conclusions:
- A new, efficient, and chemoselective method for methanesulfonamide deprotection has been established.
- This method utilizes readily available reagents (base and O(2)) and offers a valuable alternative to existing protocols.
- The findings open new avenues for sulfonamide-based synthesis and drug discovery.
Related Concept Videos
01:23Amines to Sulfonamides: The Hinsberg Test
The Hinsberg test is a method to identify primary, secondary and tertiary amines, named after its pioneer, Oscar Hinsberg. Here, amines are treated with benzenesulfonyl chloride, also known as the Hinsberg reagent, in the presence of an excess of aqueous base, followed by acidification. Based on the nature of the amines, different changes are observed.
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing sulfonyl...
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing sulfonyl...
01:17Phase II Reactions: Methylation Reactions
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
01:22Preparation of 1° Amines: Azide Synthesis
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
01:19Amines to Amides: Acylation of Amines
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
01:28Preparation of 1° Amines: Gabriel Synthesis
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
01:38Preparation of Amines: Reductive Amination of Aldehydes and Ketones
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.